Death domain containing receptor 5

Abstract

The present invention relates to novel Death Domain Containing Receptor-5 (DR5) proteins which are members of the tumor necrosis factor (TNF) receptor family, and have now been shown to bind TRAIL. In particular, isolated nucleic acid molecules are provided encoding the human DR5 proteins. DR5 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying antagonists and antagonists of DR5 activity.

What is claimed is:  
     
       1. An isolated TRAIL receptor DNA, wherein said DNA comprises the nucleotide sequence presented in SEQ ID NO:1. 
     
     
       2. An expression vector comprising a DNA according to  claim 1 . 
     
     
       3. The expression vector of  claim 2 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       4. A host cell transformed with an expression vector of  claim 2 . 
     
     
       5. The host cell of  claim 4 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       6. The DNA of  claim 1 , wherein said DNA encodes a polypeptide which binds TRAIL. 
     
     
       7. The DNA of  claim 1 , wherein said DNA encodes a polypeptide which induces apoptosis. 
     
     
       8. The DNA of  claim 1 , further comprising a heterologous DNA. 
     
     
       9. The DNA of  claim 8 , wherein said heterologous DNA encodes a heterologous polypeptide. 
     
     
       10. The DNA of  claim 9 , wherein said heterologous polypeptide comprises an immunoglobulin Fc region. 
     
     
       11. The DNA of  claim 10 , wherein said immunoglobulin Fc region is a human immunoglobulin Fc region. 
     
     
       12. A method of producing a vector that comprises inserting the DNA of  claim 1  into a vector. 
     
     
       13. A method of producing the polypeptide encoded by the DNA of  claim 1 , comprising culturing a host cell comprising said DNA under conditions such that said polypeptide is expressed, and recovering said polypeptide. 
     
     
       14. An isolated TRAIL receptor DNA, wherein said DNA encodes a polypeptide comprising amino acids −51 to 360 of SEQ ID NO:2. 
     
     
       15. An expression vector comprising a DNA according to  claim 14 . 
     
     
       16. The expression vector of  claim 15 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       17. A host cell transformed with an expression vector of  claim 15 . 
     
     
       18. The host cell of  claim 17 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       19. The DNA of  claim 14 , wherein said polypeptide induces apoptosis. 
     
     
       20. The DNA of  claim 14 , further comprising a heterologous DNA. 
     
     
       21. The DNA of  claim 20 , wherein said heterologous DNA encodes a heterologous polypeptide. 
     
     
       22. The DNA of  claim 21 , wherein said heterologous polypeptide comprises an immunoglobulin Fc region. 
     
     
       23. The DNA of  claim 22 , wherein said immunoglobulin Fc region is a human immunoglobulin Fc region. 
     
     
       24. A method of producing a vector that comprises inserting the DNA of  claim 14  into a vector. 
     
     
       25. A method of producing the polypeptide encoded by the DNA of  claim 14 , comprising culturing a host cell comprising said DNA under conditions such that said polypeptide is expressed, and recovering said polypeptide. 
     
     
       26. An isolated TRAIL receptor DNA that encodes a polypeptide capable of binding TRAIL, wherein said polypeptide comprises amino acids 1 to 360 of SEQ ID NO:2. 
     
     
       27. An expression vector comprising a DNA according to  claim 26 . 
     
     
       28. The expression vector of  claim 27 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       29. A host cell transformed with an expression vector of  claim 27 . 
     
     
       30. The host cell of  claim 29 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       31. The DNA of  claim 26 , wherein said polypeptide induces apoptosis. 
     
     
       32. The DNA of  claim 26 , further comprising a heterologous DNA. 
     
     
       33. The DNA of  claim 32 , wherein said heterologous DNA encodes a heterologous polypeptide. 
     
     
       34. The DNA of  claim 33 , wherein said heterologous polypeptide comprises an immunoglobulin Fc region. 
     
     
       35. The DNA of  claim 34 , wherein said immunoglobulin Fc region is a human immunoglobulin Fc region. 
     
     
       36. A method of producing a vector that comprises inserting the DNA of  claim 26  into a vector. 
     
     
       37. A method of producing the polypeptide encoded by the DNA of  claim 26 , comprising culturing a host cell comprising said DNA under conditions such that said polypeptide is expressed, and recovering said polypeptide. 
     
     
       38. An isolated TRAIL receptor DNA, wherein said DNA encodes a polypeptide comprising amino acids −51 to 133 of SEQ ID NO:2. 
     
     
       39. An expression vector comprising a DNA according to  claim 38 . 
     
     
       40. The expression vector of  claim 39 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       41. A host cell transformed with an expression vector of  claim 39 . 
     
     
       42. The host cell of  claim 41 , wherein said DNA is operably associated with a heterologous regulatory sequence. 
     
     
       43. The DNA of  claim 38 , further comprising a heterologous DNA. 
     
     
       44. The DNA of  claim 43 , wherein said heterologous DNA encodes a heterologous polypeptide. 
     
     
       45. The DNA of  claim 44 , wherein said heterologous polypeptide comprises an immunoglobulin Fc region. 
     
     
       46. The DNA of  claim 45 , wherein said immunoglobulin Fc region is a human immunoglobulin Fc region. 
     
     
       47. A method of producing a vector that comprises inserting the DNA of  claim 38  into a vector. 
     
     
       48. A method of producing the TRAIL receptor polypeptide encoded by the DNA of  claim 38 , comprising culturing a host cell comprising said DNA under conditions such that said polypeptide is expressed, and recovering said polypeptide.